CELLULAR AND MOLECULAR MECHANISMS OF GASTRIC-ULCER HEALING - IS THE QUALITY OF MUCOSAL SCAR AFFECTED BY TREATMENT

Background: Ulcer healing, i.e. the reconstruction of the mucosal architecture, is an active process of filling the mucosal defect with proliferating and migrating epithelial cells and connective tissue. Methods: This article represents a summary of histologic and ultrastructural assessment of the cellular events occurring during healing of experimental gastric ulcer. Results. Mucosa adjacent to the ulcer crater forms a 'healing' zone. The gastric glands in this zone dilate and the epithelial cells lining these glands de-differentiate, express epidermal growth factor receptor, and proliferate. The latter is the result of local activation of genes encoding for EGF and its receptors. At the ulcer margin, proliferating and dividing epithelial cells migrate onto the granulation tissue to cover (re-epithelialize) the ulcer and bud into granulation tissue to reconstruct glandular structures within the ulcer scar. Re-epithelialization and reconstruction of epithelial structures is under control of epidermal growth factor (EGF) and related peptides which are produced locally by regenerating cells. Under control of fibroblast growth factors, granulation connective tissue grows extensively supplying (a) microvessels for restoration of the microvascular network and (b) connective tissue cells for restoration of the lamina propria within the mucosal scar. The final outcome of the healing process reflects a dynamic interaction between the epithelial component for the 'healing' zone at the ulcer margin and the connective tissue component (including microvessels) originating from the granulation tissue. Depending on these interactions, mucosal scar can be of good quality (restoration close to normal) or poor quality. While a number of pharmacologic agents affect gastric ulcer healing, it is unknown whether these drugs affect the quality of mucosal architecture reconstruction. In previous studies, we demonstrated that sucralfate exerts a trophic effect on gastric mucosa and, compared with omeprazole, improves the quality of restored mucosal structures within the scar of healed gastric ulcers. In the most recent studies, we demonstrated that treatment with sucralfate activates genes for EGF, bFGF, and their receptors, significantly increasing (vs placebo and omeprazole) expression of EGF and its receptor in ulcerated gastric mucosa. Conclusion: Thus, the superior quality of ulcer healing by sucralfate (versus omeprazole) is most likely based on its capacity to induce and stimulate expression of EGF, bFGF, and their receptors.